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Status |
Public on May 26, 2018 |
Title |
5-hydroxymethylcytosine alterations in the human postmortem brains of autism spectrum disorder |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
Autism spectrum disorders (ASD) comprise a group of disorders characterized by impaired language, social, and communication skills, in addition to restrictive behaviors or stereotypies. However, with a prevalence of 1.5% in developed countries and relatively high comorbidity rates, no clear underlying mechanism that unifies the heterogeneous phenotypes of ASD is known. 5-hydroxymethylcytosine (5hmC) has been reported highly enriched in brain, and is now recognized as an important epigenetic mark in developmental and neurological disorders. To explore the role of 5hmC in ASD, we utilized the genomic DNA isolated from the postmortem cerebellum of both ASD patients and age-matched controls to profile genome-wide distribution of 5hmC. We identified 797 age-dependent differential hydroxymethylated regions (DhMRs) (q-value < 0.05, FDR adjusted) in young group (age ≤ 18), while no significant DhMR was identified in the groups over 18-year-old. Pathway and disease association analyses indicated that the intragenic DhMRs were located in the genes that involved in cell-cell communication and neurological disorders. By comparing the 5hmC counts (ASD vs. Control) in each psychiatric gene (±10kb), we observed significant 5hmC changes in larger fraction of psychiatric genes than in reference genes. Interestingly, we found that the predicted cis functions of non-coding intergenic DhMRs strikingly associated with ASD and intellectual disorders. A significant fraction of intergenic DhMRs were overlapped with topologically associating domains (TAD). These results together suggest that 5hmC dynamic alteration is associated with ASD, particularly in the early development stage, and could contribute to the pathogenesis of ASD.
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Overall design |
To explore the role of 5hmC in ASD, we isolated genomic DNA from the postmortem cerebellum of 17 ASD patients and 19 age-matched controls, and profiled the genome-wide 5hmC distribution by employing a previously established chemical labeling and affinity purification method, coupled with high-throughput sequencing technology. Age groups are defined as: young (< 18) , middle (18< age < 35), old (>35).
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Contributor(s) |
Cheng Y, Jin P |
Citation(s) |
29790956 |
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Submission date |
Nov 16, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Ying Cheng |
E-mail(s) |
ying.cheng@emory.edu
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Organization name |
Emory University
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Department |
Human Genetics
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Lab |
Peng Jin
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Street address |
615 Michael Street
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City |
Atlanta |
State/province |
GA |
ZIP/Postal code |
30322 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (36)
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Relations |
BioProject |
PRJNA418782 |
SRA |
SRP125126 |
Supplementary file |
Size |
Download |
File type/resource |
GSE107012_Middle.DhMRs.txt.gz |
5.2 Mb |
(ftp)(http) |
TXT |
GSE107012_Old.DhMRs.txt.gz |
6.2 Mb |
(ftp)(http) |
TXT |
GSE107012_Young.DhMRs.txt.gz |
5.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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